These studies are designed to understand the biochemical basis of drug and disease-induced extra-pyramidal motor disorders. These studies center on the stereotyped response of rodents to apomorphine as a model behavior directly relevant to human movement disorders. We will study the effect of drugs that alter the synthesis and metabolism of 5HT, Ach, and DA or interact with their specific receptors in the forebrain on this model behavior. We will also study the transmitter interactions in various regions of the forebrain by measuring their turnoverrates of these 3 transmitters after the administration of drugs that alter normal motor function. Since extrapyramidal dyskinesias may be related to the development of receptor supersensitivity, we will study this phenomenon in the CNS. We will also study amino acid analogs of DOPA that form false transmitters with weak agonist properties and consequently may have therapeutic potential. The information resulting from these experiments will be used in order to study the biochemical changes underlying the hereditary motor disease (strio-cerebellar degeneration, Mettler and Goss, 1946) of the Kerry Blue Terrier. We will attempt to determine the relationship between transmitter turnover in discrete brain regions and the motor abnormalities. On the basis of this information we will treat the abnormal symptoms in these dogs with drugs that affect synaptic function.